Department of Chemistry

Phone: (202) 994-6121 Fax: (202) 994-5873gwchem@gwu.eduE-mail:

Washington, DC 20052800 22nd street, NW | SEH 4000

Website: http://chemistry.columbian.gwu.edu

“Novel Small Molecules, Targets, and Strategies in Anti-Infective Development”

Jason K. Sello Associate Professor of Chemistry Department of Chemistry Brown University

Friday, September 8, 2017 SEH B1220 2:00 - 3:00 p.m. Refreshments will be served at 1:45 p.m.

The increasing number of infections caused by multi-drug resistant bacteria portends a public health crisis. Unfortunately, therapeutic options are limited because of a long innovation gap in the last half-century of antibacterial drug development. The gap is reflected in marketed drugs that have closely related structures and act on a few essential phenomena like DNA replication, transcription, translation, and cell envelope homeosta-sis. This situation is problematic because genetic mutations or genes that confer resis-tance to one antibacterial drug often compromise the efficacies of others with the same target or mechanism of action. To circumvent this “cross-resistance”, we must identify and validate new antibacterial drug targets. Among the most compelling of today’s antibacterial drug targets are the chaperone-dependent proteases that are known to play critical roles in bacterial physiology and pathogenicity. Interestingly, the accumulation of data that have validated these enzymes as drug targets has been coincident with discover-ies of novel small molecules that critically perturb them. This seminar will describe efforts in the Sello group to discover, design, and synthesize small molecules that lethally perturb the structures and functions of enzymes that mediate protein homeostasis in a variety of pathogenic bacteria. Additionally, efforts to develop inhibitors of chaper-one-dependent proteases for applications in cancer therapy will be discussed.

Jason K. Sello is an associate professor in the Department of Chemistry at Brown University. Prior to his appointment at Brown in 2006, Prof. Sello investigated RNA processing in Streptomyces bacteria using genetics as a visiting scientist at the John Innes Centre in Norwich, England and studied enzymes catalyzing antibiotic biosynthesis as a post-doctoral research fellow at Harvard Medical School in the laboratories of Prof. Christopher T. Walsh. He earned a Ph.D. in biophysics from Harvard University in 2002 for work in diversity-oriented chemical synthesis under the supervision of Prof. Stuart L. Schreiber and a B.S. in biology, magna cum laude, from Morehouse College in 1997. In his independent career, Prof. Sello has been synergistically using experi-mental methods from chemistry, biophysics, biochemistry, and genetics to study biological phenomena and to develop new therapeutics and microbial platforms for the conversion of plant biomass into commodity chemicals.

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Department of Chemistry Seminars